Spray drying of poorly soluble drugs from aqueous arginine solution

Abstract

Co-amorphous drug-amino acid mixtures have shown potential for improving the solid-state stability and dissolution behavior of amorphous drugs. In previous studies, however these mixtures have been produced mainly with small-scale preparation methods, or with methods that have required the use of organic solvents or other dissolution enhancers. In the present study, co-amorphous ibuprofen-arginine and indomethacin-arginine mixtures were spray dried from water. The mixtures were prepared at two drug-arginine molar ratios (1:1 and 1:2). The properties of the prepared mixtures were investigated with differential scanning calorimetry, X-ray powder diffractometry, Fourier-transform infrared spectroscopy and a 24h, non-sink, dissolution study. All mixtures exhibited a single glass transition temperature (T), evidence of the formation of homogenous single-phase systems. Fourier transform infrared spectroscopy revealed strong interactions (mainly salt formation) that account for the positive deviation between measured and estimated T values. No crystallization was observed during a 1-year stability study in either 1:1 or 1:2 mixtures, but in the presence of moisture, handling difficulties were encountered. The formation of co-amorphous salts led to improved dissolution characteristics when compared to the corresponding physical mixtures or to pure crystalline drugs.

Permeability of glibenclamide through a PAMPA membrane: The effect of co-amorphization

“…Instead, Trc was not observed for GBC-ARG. The single Tg value observed was found to be lower than for pure GBC and higher than that previously estimated for ARG (18.4°C [41], 34.0°C [32] and 55°C [53]). When SLS was added to the mixture, the value of Tg was lowered somewhat further.…”

“…Additionally, amorphous ARG salts have been prepared with several drug molecules, and similar changes in the IR peaks of ARG between the spectra of amorphous salts and amorphous ARG (i.e. shifts in the C-N stretching, COOstretching and aliphatic chain vibrations) have been observed previously [32,[40][41][42][43][44][45]. Thus, in addition to salt formation, also hydrogen bonding between GBC and ARG [46,47] as well as an interaction between the guanidinium group of ARG (vibrations at 1674 cm -1 and 1614 cm -1 in crystalline ARG) and the aromatic moiety of GBC [41,46,48,49] should be considered as a possible source for the changes in the IR spectrum of the co-amorphous GBC-ARG mixture.…”

“…These maxima, however, corresponded rather well to the wavenumbers of the guanidyl group stretching peak of amorphous ARG (Fig. 3c) at 1632 cm -1 [32] and the peaks of amorphous GBC at 1596 cm -1 and at 1531 cm -1 (urea NH bending [33]), which indicates that these changes originated mostly from the transformation from the crystalline to the amorphous form.…”

“…3., [9]). The formation of an amorphous ARG salt is known to enhance the dissolution of drugs [32,34] and furthermore, interactions of the guanidinium group of ARG with aromatic rings have been observed to increase the solubility of aromatic molecules and this has been referred to as the "arginine-assisted solubilization system" [48]. However, when the higher amount of SLS was added to the mixture, the amounts of dissolved GBC remained slightly lower.…”

Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

“…For other molar ratios, it has been observed that the co-amorphous SDs recrystallize to pure components, with the excess component crystallizing faster [ 15 , 19 ], unless other mechanisms are involved [ 24 ]. However, there have also been studies [ 35 , 55 ] showing stability for other molecular proportions. For example, 2:1, 1:1 and 1:2 compositions of tranilast-diphenhydramine systems remained amorphous during 30 days and 1: 1 and 1:2 co-amorphous dispersions of IBU-ARG and IND-ARG did not crystallize, probably due to hydrogen bonding along with salt formation, which can explain the high stability of the 1:2 composition.…”